Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: IPO7

Gene summary for IPO7

Gene summary.

Gene information	Species	Human
	Gene symbol	IPO7
	Gene ID	10527
	Gene name	importin 7
	Gene Alias	Imp7
	Cytomap	11p15.4
	Gene Type	protein-coding
	GO ID	GO:0000079
	UniProtAcc	B3KNG9

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
10527	IPO7	LZE4T	Human	Esophagus	ESCC	6.97e-06	1.88e-01	0.0811
10527	IPO7	LZE7T	Human	Esophagus	ESCC	1.85e-03	4.86e-01	0.0667
10527	IPO7	LZE8T	Human	Esophagus	ESCC	8.96e-13	1.14e-01	0.067
10527	IPO7	LZE20T	Human	Esophagus	ESCC	2.16e-12	-2.00e-01	0.0662
10527	IPO7	LZE22D1	Human	Esophagus	HGIN	5.92e-09	-2.15e-01	0.0595
10527	IPO7	LZE22T	Human	Esophagus	ESCC	3.15e-03	-8.21e-02	0.068
10527	IPO7	LZE24T	Human	Esophagus	ESCC	1.07e-08	5.09e-01	0.0596
10527	IPO7	LZE21T	Human	Esophagus	ESCC	8.33e-05	-8.41e-02	0.0655
10527	IPO7	P1T-E	Human	Esophagus	ESCC	2.69e-03	-1.23e-01	0.0875
10527	IPO7	P2T-E	Human	Esophagus	ESCC	7.40e-20	4.36e-01	0.1177
10527	IPO7	P4T-E	Human	Esophagus	ESCC	4.56e-10	1.04e-01	0.1323
10527	IPO7	P5T-E	Human	Esophagus	ESCC	1.69e-09	-5.97e-02	0.1327
10527	IPO7	P8T-E	Human	Esophagus	ESCC	1.75e-12	7.25e-02	0.0889
10527	IPO7	P9T-E	Human	Esophagus	ESCC	5.89e-11	2.36e-01	0.1131
10527	IPO7	P10T-E	Human	Esophagus	ESCC	5.88e-11	1.76e-01	0.116
10527	IPO7	P11T-E	Human	Esophagus	ESCC	5.06e-11	6.28e-01	0.1426
10527	IPO7	P12T-E	Human	Esophagus	ESCC	1.22e-23	-5.85e-02	0.1122
10527	IPO7	P15T-E	Human	Esophagus	ESCC	5.32e-26	8.31e-01	0.1149
10527	IPO7	P16T-E	Human	Esophagus	ESCC	8.12e-18	2.30e-01	0.1153
10527	IPO7	P17T-E	Human	Esophagus	ESCC	5.27e-04	5.47e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:007259420	Esophagus	HGIN	establishment of protein localization to organelle	120/2587	422/18723	1.73e-15	4.00e-13	120
GO:003450417	Esophagus	HGIN	protein localization to nucleus	84/2587	290/18723	1.06e-11	1.24e-09	84
GO:000691319	Esophagus	HGIN	nucleocytoplasmic transport	83/2587	301/18723	2.14e-10	1.97e-08	83
GO:005116919	Esophagus	HGIN	nuclear transport	83/2587	301/18723	2.14e-10	1.97e-08	83
GO:001703817	Esophagus	HGIN	protein import	51/2587	206/18723	1.79e-05	4.86e-04	51
GO:005117010	Esophagus	HGIN	import into nucleus	41/2587	159/18723	4.24e-05	1.04e-03	41
GO:000660610	Esophagus	HGIN	protein import into nucleus	39/2587	155/18723	1.14e-04	2.39e-03	39
GO:004593626	Esophagus	HGIN	negative regulation of phosphate metabolic process	89/2587	441/18723	1.24e-04	2.54e-03	89
GO:001056326	Esophagus	HGIN	negative regulation of phosphorus metabolic process	89/2587	442/18723	1.34e-04	2.71e-03	89
GO:004232620	Esophagus	HGIN	negative regulation of phosphorylation	78/2587	385/18723	2.77e-04	4.77e-03	78
GO:000193320	Esophagus	HGIN	negative regulation of protein phosphorylation	69/2587	342/18723	6.81e-04	9.26e-03	69
GO:005134827	Esophagus	HGIN	negative regulation of transferase activity	55/2587	268/18723	1.51e-03	1.74e-02	55
GO:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273
GO:0051348111	Esophagus	ESCC	negative regulation of transferase activity	177/8552	268/18723	1.08e-11	4.00e-10	177

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa030133	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa030134	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa030135	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

IPO7

SNV

Missense_Mutation

rs773555364

c.2413N>T

p.Arg805Cys

p.R805C

O95373

protein_coding

deleterious(0.04)

benign(0.006)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.2403A>T

p.Leu801Phe

p.L801F

O95373

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-D8-A1X8-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adrimicin+cyclophosphamide

IPO7

deletion

Frame_Shift_Del

novel

c.788delN

p.Ala264ProfsTer5

p.A264Pfs*5

O95373

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

IPO7

SNV

Missense_Mutation

c.2248A>G

p.Lys750Glu

p.K750E

O95373

protein_coding

deleterious(0.01)

possibly_damaging(0.805)

TCGA-EA-A5FO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.1564N>G

p.Gln522Glu

p.Q522E

O95373

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-EK-A2R7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.3044G>T

p.Gly1015Val

p.G1015V

O95373

protein_coding

deleterious(0)

benign(0.156)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IPO7

SNV

Missense_Mutation

novel

c.21N>G

p.Ile7Met

p.I7M

O95373

protein_coding

deleterious(0.01)

possibly_damaging(0.681)

TCGA-MA-AA3Y-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IPO7

SNV

Missense_Mutation

novel

c.2849N>C

p.Asp950Ala

p.D950A

O95373

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.1976C>T

p.Ala659Val

p.A659V

O95373

protein_coding

tolerated(1)

benign(0.042)

TCGA-VS-A9V4-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IPO7

SNV

Missense_Mutation

novel

c.2411N>G

p.Leu804Arg

p.L804R

O95373

protein_coding

deleterious(0)

possibly_damaging(0.786)

TCGA-A6-3808-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
10527	IPO7	NA		MKC-1	ENMD-981693

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